Sustained release formulation, particularly in tablet and in capsule forms, is a very useful formulation that can reduce the frequency of administration and can control drug level in blood to sustain pharmacological effect. For example, sustained release formulation can change the dose frequency of the drugs such as ibuprofen, phenylpropanolamine hydrochloride, fluvastatin, lovastatin and so on from several times daily in general to once or twice daily.
As a method of preparing a sustained release formulation, it is widely recognized that various hydrophilic polymer materials can be used as sustained release matrix. For example, a fluvastatin sustained-release tablet, described in CN Pat. No. ZL 200780014499.X and CN Pat. No. ZL 99812081.2, is prepared by comprising active pharmaceutical ingredients, water encounter swelling hydrophilic structural materials and other excipients. When this medicine is taken, water insinuates into tablet to dissolve active pharmaceutical ingredients, and make hydrophilic structural materials swell to form high viscosity gel; then the dissolved pharmaceuticals can be delayed-released through the high viscosity gel. At present, sustained release formulation have a high amount of hydrophilic polymer materials in general, water encounter swelling of which easily causes problems in the production and storage of drugs, such as more waste produced, difficulty to form film coating or that the stability of some drugs is affected in storage since sustained release tablets absorb water easily.
As another method, that osmotic pump technology is used to prepare sustained release formulation is disclosed in prior art, such as a lovastatin sustained-release tablet described in U.S. Pat. No. 5,916,595. In this method, active pharmaceutical ingredients, osmotic pressure regulators and other excipients are prepared the tablet core; since lovastatin is practically insoluble in water, all the materials in the tablet core should be hydrophilic, which causes producing more waste, making film coating difficult and easily absorbing water to affect drug stability. In addition, large amounts of organic solvents should be used to dissolve coating materials when the tablet core film-coating. The use of large amounts of organic solvents in drug production is easy to cause environmental pollution and security risks. Laser drilling, the process of which is complicate and the rejection rate of which is high, is needed after film coating.
Generally, the sustained release formulation contains low water-soluble even water-insoluble active pharmaceutical ingredients, which excipient materials especially the sustained-release structural materials are all hydrophilic. In addition, for high water-soluble, low water-soluble even water-insoluble active pharmaceutical ingredients, the preparation of sustained release formulation containing heavy doses of the active pharmaceutical ingredients is very difficult.
For the active pharmaceutical ingredients having lower or higher pKa value, the pH of dissolution medium has great influence on solubility and dissolution of drugs, so the preparation of sustained release formulation having high content of the active pharmaceutical ingredients is also very difficult.
Therefore, it is necessary to develop new sustained release formulations to solve one or more problems in prior art.